A genome-wide association study based on the China Kadoorie Biobank identifies genetic associations between snoring and cardiometabolic traits

Despite the high prevalence of snoring in Asia, little is known about the genetic etiology of snoring and its causal relationships with cardiometabolic traits. Based on 100,626 Chinese individuals, a genome-wide association study on snoring was conducted. Four novel loci were identified for snoring traits mapped on SLC25A21, the intergenic region of WDR11 and FGFR, NAA25, ALDH2, and VTI1A, respectively. The novel loci highlighted the roles of structural abnormality of the upper airway and craniofacial region and dysfunction of metabolic and transport systems in the development of snoring. In the two-sample bi-directional Mendelian randomization analysis, higher body mass index, weight, and elevated blood pressure were causal for snoring, and a reverse causal effect was observed between snoring and diastolic blood pressure. Altogether, our results revealed the possible etiology of snoring in China and indicated that managing cardiometabolic health was essential to snoring prevention, and hypertension should be considered among snorers.


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Canqing Yu
The GWAS summary statistics from China Kadoorie Biobank (CKB) in the present study have been deposited in the Genome In the CKB study, Extensive questionnaire data, physical measurements, and blood samples were collected upon baseline assessment in 2004-2008, led by trained investigators.Blood samples were used for genotyping.Two resurveys were conducted in 2008 and 2013-2014, which involved ~5% randomly chosen surviving participants.
The descriptive analysis was conducted with STATA version 16.0.The GWAS analysis used the BOLT-LMM 2.3.2 linear mixed model.Fixed-effect inverse-variance-weighted Meta-analysis including ten study areas was conducted using METAL.Genomic risk loci were identified by PLINK 1.9.The positional mapping and annotation were conducted via ANNOVAR.The eQTL mapping was conducted using the Genotype-Tissue Expression database (http://www.gtexportal.org/home/).The relationship between each of the prioritized genes and tissues, and enrichment analysis were conducted with FUMA GENE2FUNC.A two-sided Mann-Whitney U test for MAF comparison was conducted with R 4.0.5.PRSice-2 was used for PRS conduction.LDSC (version 1.0.1) was applied to estimate SNP-based heritability and genetic correlation.R packages "TwoSampleMR (version 0.5.6)" and "MRPRESSO (version 1.0)" were used for MR analysis.
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CKB study is a prospective cohort study that recruited 512,715 adults aged 30-79 years living in 10 study areas across China.
Among CKB participants (n=100,626), 46.9% were snorers, including 22,985 (22.8%) habitual snorers.Snoring frequency differed in the ten study areas.55.0% of males and 40.9% of females were snorers.The habitual snorers were more likely to be elders, males, with geographical origins in the south of China, with the same geographical and ancestry origins, with higher BMI, WC, and blood pressure, and more likely to be weekly drinkers and current smokers (all P<0.05).
CKB study is a prospective cohort study that recruited 512,715 adults aged 30-79 years living in 10 study areas across China.
The study protocol was approved by the Ethics Review Committee of the Chinese Center for Disease Control and Prevention (Beijing, China: 005/2004) and the Oxford Tropical Research Ethics Committee, University of Oxford (UK: 025-04).All participants provided written informed consent before taking part in the study.
Please select the one below that is the best fit for your research.The present study included participants with no missing values of snoring phenotype or genotype and passed pre-imputation quality control (QC) (n=100,640).Participants who failed sex QC or missed data were excluded, leaving 100,626 participants for GWAS of snoring.
To test the validity of our results, an independent replication in the UKB GWAS of snoring was performed, with a sample size of 408,317 participants (152,000 snoring cases).Besides, a replication analysis for snoring risk loci identified in UKB was also conducted with the CKB GWAS of snoring If you are not sure, read the appropriate sections before making your selection.
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